The present invention relates to vitamin D compounds, and more particularly to the use of 1.alpha.-hydroxylated-19-nor-vitamin D compounds to treat psoriasis.
The D vitamins are very important agents for the control of calcium and phosphate metabolism in animals and humans, and have long been used as dietary supplements and in clinical practice to assure proper bone growth and development. It is now known that the in vivo activity of these vitamins, specifically of vitamin D.sub.2 and D.sub.3, is dependent on metabolism to hydroxylated forms. Thus, vitamin D.sub.3 undergoes two successive hydroxylation reactions in vivo, leading first to 25-hydroxyvitamin D.sub.3 and then to 1,25-dihydroxyvitamin D.sub.3 and the latter is indeed thought to be the compound responsible for the well-known beneficial effects of vitamin D.sub.3. Likewise, vitamin D.sub.2, which is commonly used as a dietary supplement, undergoes an analogous hydroxylation sequence to its active forms, being first converted to 25-hydroxyvitamin D.sub.2 (25--OH--D.sub.2) and then to 1,25-dihydroxyvitamin D.sub.2 (1,25--(OH).sub.2 D.sub.2). These facts are well established and well known in the art (see, for example, Suda et al. Biochemistry 8, 3515 (1969) and Jones et al. Biochemistry 14, 1250 (1975)).
Hollick, U.S. Pat. No. 4,728,643 discloses a method of treating psoriasis with vitamin D compounds which in vitro cause cell differentiation. However 1.alpha.-hydroxylated vitamin D compounds, i.e. those compounds having only a hydroxyl group at the carbon 1 position and initially lacking a hydroxyl group at the carbon 24 or 25 positions, are relatively inactive in causing cell differentiation in vitro. Additionally, it is also well known that 1.alpha.-hydroxylated compounds are rapidly converted in vivo to 1.alpha.,25-dihydroxy compounds, e.g. 1.alpha.-hydroxyvitamin D.sub.3 to 1.alpha.,25-dihydroxy-vitamin D.sub.3, or if the 25 carbon position is blocked to 1.alpha.,24-dihydroxy compounds. Hollick et al, Science, Vol. 190, pages 576-578 (1975) and Hollick et al, J. of Clinical Endocrinology & Metabolism, Vol. 44, pages 595-598 (1977). For example, in PCT patent application number PCT/DK89/00079 filed Apr. 7, 1989 and published Nov. 2, 1989 under number WO89/10351 there is disclosed numerous side chain homologated vitamin D compounds lacking the hydroxyl group at the carbon 25 position in the side chain. It is disclosed therein that such compounds are converted in vivo to active compounds having a hydroxyl group at the carbon 25 position by enzymatic hydroxylation, and may thus be used for the treatment of psoriasis. Thus, the human body can rapidly convert relatively inactive 1.alpha.-hydroxylated vitamin D compounds to metabolites highly active in causing cell differentiation. There has, however, been a failure in the art to recognize the ability of 1.alpha.-hydroxylated-19-nor-vitamin D compounds to treat malignancies such as psoriasis.